title: Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients.
abstract: This study tested the hypothesis that the expression of CD112 and CD155 (DNAM-1 ligands) on leukemic blasts induces a decreased expression of the activating receptor DNAM-1 on natural killer (NK) cells from acute myeloid leukemia (AML) patients. DNAM-1 is a co-receptor involved in the activation of NK cell cytotoxicity after its interaction with its ligands CD112 and CD155 on target cells. Here we study the expression of DNAM-1 on NK cells and DNAM-1 ligands on blasts from AML patients stratified by age. The results demonstrate that NK cells from AML patients younger than 65 years have a reduced expression of DNAM-1 compared with age-matched controls. The analysis of DNAM-1 ligands showed a high expression of CD112 and CD155 on leukemic blasts. An inverse correlation between CD112 expression on leukemic blasts and DNAM-1 expression on NK cells was found. Furthermore, downregulation of DNAM-1 was induced on healthy donors' NK cells after in vitro culture with leukemic blasts expressing DNAM-1 ligands. In conclusion, these results support the hypothesis that receptor-ligand crosslinking downregulates DNAM-1 expression on NK cells from patients <65 years of age. Considering the relevance of DNAM-1 in NK recognition and killing of leukemic cells, the reduced expression of this receptor on NK cells from AML patients can represent an additional mechanism of tumor escape.
authors.affiliation: Immunology Unit, Department of Physiology, University of Extremadura, Caceres, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanchez-Correa
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Gayoso
authors.forename: Juan M
authors.initials: JM
authors.lastname: Bergua
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
authors.forename: Sara
authors.initials: S
authors.lastname: Morgado
authors.forename: Rafael
authors.initials: R
authors.lastname: Solana
authors.forename: Raquel
authors.initials: R
authors.lastname: Tarazona
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D000075983:Nectins; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011991:Receptors, Virus / Q000096:biosynthesis / Q000276:immunology*; D055815:Young Adult; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D015815:Cell Adhesion Molecules; D008024:Ligands; D000075983:Nectins; D011991:Receptors, Virus; C066100:poliovirus receptor